The burden of chronic liver disease in west Africa: a time for action
Authors: Catherine Wendy Spearman
Journal: The Lancet Global Health (2023)

The burden of chronic liver disease in sub-Saharan Africa is high, with cirrhosis and other chronic liver diseases accounting for 2·5% of deaths and 1·3% of total disability-adjusted life-years in 2019.1GBD 2019 Diseases and Injuries CollaboratorsGlobal burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet. 2020; 396120422Google Scholar The most prevalent causes of cirrhosis and hepatocellular carcinoma in sub-Saharan Africa are chronic viral hepatitis (hepatitis B, C, and D), heavy alcohol use, aflatoxin B1 exposure, and, increasingly, metabolic risk factors associated with metabolic dysfunction-associated steatotic liver disease (MASLD).2Devarbhavi H Asrani SK Arab JP Nartey YA Pose E Kamath PS Global burden of liver disease: 2023 update.J Hepatol. 2023; 79: 516-537Summary Full Text Full Text PDF PubMed Google Scholar Concerningly, most patients with hepatocellular carcinoma in the region present with inoperable, multifocal disease (Barcelona Clinic Liver Cancer Classification Stage C–D), reflecting limited access to point-of-care serological and molecular diagnostics, screening and surveillance programmes, and early linkage to appropriate care.3Yang JD Mohamed EA Aziz AO et al.Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa Liver Cancer Consortium.Lancet Gastroenterol Hepatol. 2017; 2: 103-111Summary Full Text Full Text PDF PubMed Scopus (129) Google Scholar All these drivers of cirrhosis and hepatocellular carcinoma are potentially preventable or treatable, but they need to be recognised and addressed as a public health priority. In west Africa, the age-standardised incidence rate (ASIR) for cirrhosis is 26·22 cases (95% uncertainty interval [UI] 19·92–33·23) per 100 000 population and age-standardised death rate (ASDR) is 37·5 deaths (95% UI 30·28–46·47) per 100 000 population, with hepatitis B causing 43% of deaths.1GBD 2019 Diseases and Injuries CollaboratorsGlobal burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet. 2020; 396120422Google Scholar West Africa has the highest burden of hepatocellular carcinoma in sub-Saharan Africa, with an ASIR of 8·4 cases per 100 000 population and an ASDR of 8·2 cases per 100 000 population.4Sung H Ferlay J Siegel RL et al.Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cCancers in 185 countries.CA Cancer J Clin. 2021; 71: 209-249Crossref PubMed Scopus (0) Google Scholar After Guinea, The Gambia has the highest ASIR and ASDR in sub-Saharan Africa (17·2 cases and 16.8 deaths per 100 000, respectively).4Sung H Ferlay J Siegel RL et al.Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cCancers in 185 countries.CA Cancer J Clin. 2021; 71: 209-249Crossref PubMed Scopus (0) Google Scholar Hepatocellular carcinoma also presents at a young age in west Africa, with the mean age of diagnosis being 40 years in The Gambia.5Bittaye SO Njie R Tekanyi M et al.Abstract 2346: Clinical manifestation, staging and prognosis of hepatocellular carcinoma in Gambian patients.Cancer Research. 2020; 802346Crossref Google Scholar Longitudinal studies from sub-Saharan Africa on the natural history and outcomes of cirrhosis are scarce. In The Lancet Global Health, Gibril Ndow and colleagues present an important prospective study, in which they analysed the clinical characteristics and outcomes of 336 patients with cirrhosis (n=84) and hepatocellular carcinoma (n=252); and the effectiveness of tenofovir disoproxil fumarate (TDF) in The Gambia.6Ndow G Quang EV Shimakawa Y et al.Clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia, west Africa: a prospective cohort study.Lancet Glob Health. 2023; (published online July 27.)https://doi.org/10.1016/S2214-109X(23)00263-2Google Scholar In this study, 75·3% of patients were men and median age was 42 years (IQR 33–55). Based on serology, 84% of patients had antibodies against hepatitis B virus (HBV), 10% had antibodies against hepatitis C virus (HCV), and 10% had antibodies against hepatitis D virus (HDV). Of concern, despite The Gambia being the first African country to integrate HBV vaccination into its national infant immunisation programme starting immediately after birth, hepatitis B infection remains the main cause of cirrhosis and hepatocellular carcinoma, with more than two-thirds of the study population being positive for HBV. These findings are in line with a systemic review showing that an early age of chronic hepatitis B infection is associated with increased risk of cirrhosis and hepatocellular carcinoma.7Shimakawa Y Yan HJ Tsuchiya N Bottomley C Hall AJ Association of early age at establishment of chronic hepatitis B infection with persistent viral replication, liver cirrhosis and hepatocellular carcinoma: a systematic review.PLoS One. 2013; 8e69430Crossref PubMed Scopus (47) Google Scholar, 8Shimakawa Y Lemoine M Njai HF et al.Natural history of chronic HBV infection in West Africa: a longitudinal population-based study from The Gambia.Gut. 2016; 65: 2007-2016Crossref PubMed Scopus (102) Google Scholar According to WHO/UNICEF data, in 2020, 26·1% of newborn babies received an HBV vaccination dose within 24 h of delivery, compared with 35% in 2019 and 98% in 2015. The coverage of a third dose of HBV vaccine has decreased from 97% in 2015 to 79% in 2020.9UNICEF-WHOHepatitis B Vaccine Coverage.https://www.who.int/teams/immunization-vaccines-and-biologicals/immunization-analysis-and-insights/global-monitoring/immunization-coverage/who-unicef-estimates-of-national-immunization-coverageDate: 2022Date accessed: July 13, 2023Google Scholar These data further emphasise the need to improve and maintain overall coverage and timely delivery of the cancer-preventing HBV vaccine. Occult hepatitis B infection (OBI) has previously been shown to be an independent risk factor for advanced liver disease in The Gambia,10Ndow G Cessay A Cohen D et al.Prevalence and clinical significance of occult hepatitis B infection in The Gambia, West Africa.J Infect Dis. 2022; 226: 862-870Crossref PubMed Scopus (3) Google Scholar and it is often an unrecognised risk factor for the development of hepatocellular carcinoma. Of note, in this study, OBI was found in patients who were negative for hepatitis B surface antigen (HBsAg) with cirrhosis (43%) or hepatocellular carcinoma (53%), further emphasising the need for an effective hepatitis B vaccination programme and prevention of early-life acquisition of hepatitis B. HDV infection is associated with accelerated progression to cirrhosis and increased incidence of hepatocellular carcinoma. Natural history data have not been reported in African populations for HDV genotypes 5–8, which are specific to Africa. HDV antibodies were detected in 8·1% and 14·3% of patients with hepatocellular carcinoma and cirrhosis, respectively, in this study. These HDV antibody rates were much higher than the estimated HDV prevalence of 2% among community-screened HBsAg-positive adults in The Gambia. Although confirmatory HDV RNA testing for active infection was not performed, present assays for Africa-specific genotypes 5–8 often report false-negative results. With the recommendation of reflex anti-HDV testing to increase diagnosis of HDV and the promise of effective new anti-HDV therapeutics such as bulevirtide, it will be essential to standardise HDV screening serological tests and improve access to sensitive pangenotypic HDV RNA testing in Africa. The median survival was 17·1 months for patients with compensated cirrhosis, 11·3 months for those with decompensated cirrhosis, and 1·5 months for those with hepatocellular carcinoma. The median turnaround time between the first diagnosis of HBV-related cirrhosis and initiation of tenofovir was 4·9 months (IQR 3·2–7·3). Half of the HBV-related patients with cirrhosis were either lost to follow-up or did not return to clinic for reassessment and treatment initiation; with the delay in initiation associated with turnaround time for results including HBV DNA quantification. Importantly, TDF treatment was associated with improved survival in patients with HBV-related cirrhosis (IPTW-adjusted Cox analysis HR 0·14; 95% Cl 0·06–0·34, p<0·0001). With TDF costing less than US$50 per year, treatment should be offered to all patients with HBV-related cirrhosis regardless of HBV DNA levels. The 2-year survival rate of 71% was below the 1-year and 3-year cumulative probability of survival from liver-related deaths (99·4% and 97·8%, respectively) reported in European and North American, and Asian studies. 68% of patients already had decompensated cirrhosis at presentation and patients with hepatocellular carcinoma presented late, with 64% having inoperable multifocal tumours. The study emphasises the urgent need in west Africa for simplified treatment guidelines for viral hepatitis adapted to resource-limited settings, where affordable point-of-care diagnostics and antiviral therapy for hepatitis B, C and D as well as early assessment of severity of disease and accessible pathways to care are a public health priority. I have received Speaker Bureau fees from GILEAD Sciences and Abbott. Clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia, west Africa: a prospective cohort studyThese results highlight poor survival of patients with cirrhosis or hepatocellular carcinoma as well as the effectiveness of TDF in reducing the premature mortality of patients with cirrhosis and HBV infection. Interventions for early diagnosis and treatment of cirrhosis as well as screening programmes for hepatocellular carcinoma are urgently required in Africa. Full-Text PDF Open Access